CPA-ready femtosecond pulses at 1 MHz from a custom recycled output Mamyshev oscillator.

A cost-effective fiber laser architecture is introduced in which the output seed pulse is stretched and then returned in the oscillator for an additional single-pass amplification without spectral broadening. It is implemented in an all-PM-fiber configuration based on a Mamyshev oscillator with a low repetition rate of 1 MHz. It features a linear oscillator bounded by two offset chirped fiber Bragg gratings accompanied by a third one acting as a pulse recycling filter. The latter tailors the pulse profile in amplitude and phase to seed femtosecond chirped-pulse amplification systems without additional pre-amplification nor pulse stretching. A single-pump prototype generating 200-nJ, 100-ps pulses compressible to 290 fs at 1030 nm and at 960 kHz is demonstrated. Furthermore, simulations show how this new oscillator architecture can provide tailored seed pulses with high enough spectral energy density and low enough nonlinear phase to generate sub-200 fs, 40 µJ, > 180 MW pulses from an all-fiber setup involving a single tapered-fiber power amplifier, without pulse picking.

Femtosecond Mamyshev oscillator at 920 nm.

A femtosecond all-PM-fiber Mamyshev oscillator (MO) at 920 nm is presented. It is based on a neodymium-doped fiber with a W-type index profile that effectively suppresses the emission around 1064 nm. The linear cavity is bounded by two near-zero dispersion fiber Bragg gratings with Gaussian reflectivity profiles. The laser is self-starting and generates up to 10-nJ pulses at a repetition rate of 41 MHz. The pulses can be compressed to 53 fs with a grating-pair compressor. To our knowledge, this is the first Mamyshev oscillator and also the highest energy femtosecond fiber oscillator demonstrated in this spectral region.

Visible femtosecond fiber laser.

Femtosecond fiber lasers have revolutionized the industry of laser technology by providing ultrashort pulses of high brightness through compact, affordable, and reliable setups. In this work, we extend the scope of application of such sources by reporting, to our knowledge, the first femtosecond fiber laser operating in the visible spectrum. The passively mode-locked ring cavity is based on nonlinear polarization evolution in a single-mode Pr3+-doped fluoride fiber and runs in an all-normal dispersion regime. Compressed pulses at 635 nm have a duration of 168 fs, a peak power of 0.73 kW, and a repetition rate of 137 MHz.

Multi-megawatt pulses at 50 MHz from a single-pump Mamyshev oscillator gain-managed amplifier laser.

We have developed a compact all-PM-fiber ytterbium-doped Mamyshev oscillator-amplifier laser system generating compressed pulses of 102 nJ and 37 fs, thus having over 2 MW of peak power, at a repetition rate of 52 MHz. The pump power from a single diode is shared between a linear cavity oscillator and a gain-managed nonlinear amplifier. The oscillator is self-started by pump-modulation and a linearly polarized single-pulse operation is achieved without filter tuning. The cavity filters are near-zero dispersion fiber Bragg gratings with a Gaussian spectral response. To our knowledge, this simple and efficient source has the highest repetition rate and average power among all-fiber multi-megawatt femtosecond pulsed laser sources and its architecture holds potential for generating higher pulse energies.

Femtosecond tunable solitons up to 4.8 µm using soliton self-frequency shift in an InF3 fiber.

A tunable ultrashort soliton pulse source reaching up to 4.8 µm is demonstrated based on a 2.8 µm femtosecond fiber laser coupled to a zirconium fluoride fiber amplifier followed by a small core indium fluoride fiber. This demonstration is extending by 300 nm the long wavelength limit previously reported with soliton self-frequency shift (SSFS) sources based on fluoride fibers. Our experimental and numerical investigation highlighted the spectral dynamics associated with the generation of highly redshifted pulses in the mid-infrared using SSFS enhanced by soliton fission. This study is intended at providing a better understanding of the potential and limitations of SSFS based tunable femtosecond fiber sources in the 3-5  µm spectral range.

Airway Administration of Flagellin Regulates the Inflammatory Response to Pseudomonas aeruginosa.

Excessive lung inflammation and airway epithelial damage are hallmarks of human inflammatory lung diseases, such as cystic fibrosis (CF). Enhancement of innate immunity provides protection against pathogens while reducing lung-damaging inflammation. However, the mechanisms underlying innate immunity-mediated protection in the lung remain mysterious, in part because of the lack of appropriate animal models for these human diseases. TLR5 (Toll-like receptor 5) stimulation by its specific ligand, the bacterial protein flagellin, has been proposed to enhance protection against several respiratory infectious diseases, although other cellular events, such as calcium signaling, may also control the intensity of the innate immune response. Here, we investigated the molecular events prompted by stimulation with flagellin and its role in regulating innate immunity in the lung of the pig, which is anatomically and genetically more similar to humans than rodent models. We found that flagellin treatment modulated NF-κB signaling and intracellular calcium homeostasis in airway epithelial cells. Flagellin pretreatment reduced the NF-κB nuclear translocation and the expression of proinflammatory cytokines to a second flagellin stimulus as well as to Pseudomonas aeruginosa infection. Moreover, in vivo administration of flagellin decreased the severity of P. aeruginosa-induced pneumonia. Then we confirmed these beneficial effects of flagellin in a pathological model of CF by using ex vivo precision-cut lung slices from a CF pigz model. These results provide evidence that flagellin treatment contributes to a better regulation of the inflammatory response in inflammatory lung diseases such as CF.

Rck of Salmonella Typhimurium Delays the Host Cell Cycle to Facilitate Bacterial Invasion.

Salmonella Typhimurium expresses on its outer membrane the protein Rck which interacts with the epidermal growth factor receptor (EGFR) of the plasma membrane of the targeted host cells. This interaction activates signaling pathways, leading to the internalization of Salmonella. Since EGFR plays a key role in cell proliferation, we sought to determine the influence of Rck mediated infection on the host cell cycle. By analyzing the DNA content of uninfected and infected cells using flow cytometry, we showed that the Rck-mediated infection induced a delay in the S-phase (DNA replication phase) of the host cell cycle, independently of bacterial internalization. We also established that this Rck-dependent delay in cell cycle progression was accompanied by an increased level of host DNA double strand breaks and activation of the DNA damage response. Finally, we demonstrated that the S-phase environment facilitated Rck-mediated bacterial internalization. Consequently, our results suggest that Rck can be considered as a cyclomodulin with a genotoxic activity.

All-fiber Mamyshev oscillator enabled by chirped fiber Bragg gratings.

We present a linear cavity self-polarizing Mamyshev oscillator at 1550 nm made fully of polarization-maintaining fibers. The cavity filters are chirped fiber Bragg gratings with a Gaussian reflectivity profile that allow for greater reflectivity, larger bandwidth, and dispersion control. This mode-locked fiber laser architecture shows an unprecedented simplicity while delivering 21.3-nJ pulses compressed to 108 fs with a competitive 22.3% pump conversion efficiency. Mode locking is initiated with an external saturable absorber mirror. Numerical simulations show how nonlinearity can be managed with highly dispersive filters inside a Mamyshev oscillator.

Surgery of single ventricles in humanitarian practice: surgery for which patients?

OBJECTIVES: To analyse the feasibility and effectiveness in humanitarian practice of surgical management of children with single-ventricle heart condition. METHODS: Retrospective study of children with a single ventricle, managed by the association Mécénat-Chirurgie Cardiaque since 1996, with long-term follow-up after their return home. RESULTS: Of the 138 children in our cohort, 119 had one or more surgeries (180 procedures): palliative surgery alone (systemic-pulmonary anastomosis or banding), 41; partial cavo-pulmonary connection, 47; total cavo-pulmonary connection (mean age 8.5 years), 31. Operative mortality is 5.5%. After a mean follow-up of 5.6 years, 18 children (13%) were lost to follow-up. Survival at 10 years is 79% in children receiving surgery (palliative only, 72%; partial cavo-pulmonary connection, 77%; total cavo-pulmonary connection, 97%) versus 29% in children with no surgical intervention. The prognosis is better for tricuspid atresia and double-inlet left ventricle (86 and 83% survival at 10 years) than for double-outlet right ventricle or complete atrio-ventricular canal defect (64 and 68% at 5 years). CONCLUSION: The surgery of the single ventricle in humanitarian medicine allows a very satisfactory survival after one or more surgeries tending towards a total cavo-pulmonary connection as soon as possible.

Revision of expert panel's guidelines on postoperative pain management.

The French Society of Anaesthesia and Intensive Care Medicine (SFAR) published experts' guidelines on the care of postoperative pain. This was an update of the 2008 guidelines. Fourteen experts analysed the literature (PubMed™, Cochrane™) on questions that had not been treated in the previous guidelines, or to modify the guidelines following new data in the published literature. The used method is invariably the GRADE© method, which guarantees a rigorous work. Seventeen recommendations were formalised on the assessment of perioperative pain, and most particularly in non-communicating patients, on opioid and non-opioid analgesics and on anti-hyperalgesic drugs, such as ketamine and gabapentinoids, as well as on local and regional anaesthesia. The concept of vulnerability and therefore the identification of the most fragile patients in terms of analgesics requirements were specified. Because of the absence of sufficient data or new information, no recommendation was made about analgesia monitoring, the procedures for the surveillance of patients in conventional care structures, or perinervous or epidural catheterism.

Femtosecond fiber Mamyshev oscillator at 1550 nm.

We investigated the possibility of reaching nanojoule-level pulse energies in a femtosecond erbium-doped fiber Mamyshev oscillator. In experiments, lasers generate stable pulse trains with energy up to 31.3 nJ, which is comparable to the highest achieved by prior ultrafast erbium fiber lasers. The pulse duration after a grating compressor is around 100 fs. However, as the pulse energy increases, the pulse quality degrades significantly, with a substantial fraction of the energy going into a picosecond pedestal. Numerical simulations agree with the experimental observations, and allow us to identify the gain spectrum and the nonlinearity of the erbium-doped fibers as challenges to the operation of such oscillators at high pulse energy.

Self-seeded, multi-megawatt, Mamyshev oscillator.

We demonstrate a fiber oscillator that achieves 3 MW peak power, is easily started, and is environmentally stable. The Mamyshev oscillator delivers 190-nJ pulses that can be compressed externally to 35 fs duration. Accurate numerical modeling of the gain medium provides insight into the behavior and performance of the device.

The Pig: A Relevant Model for Evaluating the Neutrophil Serine Protease Activities during Acute Pseudomonas aeruginosa Lung Infection.

The main features of lung infection and inflammation are a massive recruitment of neutrophils and the subsequent release of neutrophil serine proteases (NSPs). Anti-infectious and/or anti-inflammatory treatments must be tested on a suitable animal model. Mice models do not replicate several aspects of human lung disease. This is particularly true for cystic fibrosis (CF), which has led the scientific community to a search for new animal models. We have shown that mice are not appropriate for characterizing drugs targeting neutrophil-dependent inflammation and that pig neutrophils and their NSPs are similar to their human homologues. We induced acute neutrophilic inflammatory responses in pig lungs using Pseudomonas aeruginosa, an opportunistic respiratory pathogen. Blood samples, nasal swabs and bronchoalveolar lavage fluids (BALFs) were collected at 0, 3, 6 and 24 h post-insfection (p.i.) and biochemical parameters, serum and BAL cytokines, bacterial cultures and neutrophil activity were evaluated. The release of proinflammatory mediators, biochemical and hematological blood parameters, cell recruitment and bronchial reactivity, peaked at 6h p.i.. We also used synthetic substrates specific for human neutrophil proteases to show that the activity of pig NSPs in BALFs increased. These proteases were also detected at the surface of lung neutrophils using anti-human NSP antibodies. Pseudomonas aeruginosa-induced lung infection in pigs results in a neutrophilic response similar to that described for cystic fibrosis and ventilator-associated pneumonia in humans. Altogether, this indicates that the pig is an appropriate model for testing anti-infectious and/or anti-inflammatory drugs to combat adverse proteolytic effects of neutrophil in human lung diseases.

Watt-level fiber-based femtosecond laser source tunable from 2.8 to 3.6 µm.

The development of compact and reliable ultrafast sources operating in the mid-infrared region could lead to major advances in both fundamental and applied sciences. In this Letter, we report on a simple and efficient laser system based entirely on erbium-doped fluoride glass fibers that generates high-energy Raman soliton pulses tunable from 2.8 to 3.6 µm at a high average output power. Stable 160 fs pulses at 3.4 µm with a maximum energy of 37 nJ, a corresponding average output power above 2 W, and an estimated peak power above 200 kW are demonstrated. This tunable source promises direct applications in laser processing of polymers and biological materials.

Automation of Mode Locking in a Nonlinear Polarization Rotation Fiber Laser through Output Polarization Measurements.

When a laser is mode-locked, it emits a train of ultra-short pulses at a repetition rate determined by the laser cavity length. This article outlines a new and inexpensive procedure to force mode locking in a pre-adjusted nonlinear polarization rotation fiber laser. This procedure is based on the detection of a sudden change in the output polarization state when mode locking occurs. This change is used to command the alignment of the intra-cavity polarization controller in order to find mode-locking conditions. More specifically, the value of the first Stokes parameter varies when the angle of the polarization controller is swept and, moreover, it undergoes an abrupt variation when the laser enters the mode-locked state. Monitoring this abrupt variation provides a practical easy-to-detect signal that can be used to command the alignment of the polarization controller and drive the laser towards mode locking. This monitoring is achieved by feeding a small portion of the signal to a polarization analyzer measuring the first Stokes parameter. A sudden change in the read out of this parameter from the analyzer will occur when the laser enters the mode-locked state. At this moment, the required angle of the polarization controller is kept fixed. The alignment is completed. This procedure provides an alternate way to existing automating procedures that use equipment such as an optical spectrum analyzer, an RF spectrum analyzer, a photodiode connected to an electronic pulse-counter or a nonlinear detecting scheme based on two-photon absorption or second harmonic generation. It is suitable for lasers mode locked by nonlinear polarization rotation. It is relatively easy to implement, it requires inexpensive means, especially at a wavelength of 1550 nm, and it lowers the production and operation costs incurred in comparison to the above-mentioned techniques.

Vector similariton erbium-doped all-fiber laser generating sub-100-fs nJ pulses at 100 MHz.

Erbium-doped mode-locked fiber lasers with repetition rates comparable to those of solid-state lasers and generating nJ pulses are required for many applications. Our goal was to design a fiber laser that would meet such requirements, that could be built at relatively low cost and that would be reliable and robust. We thus developed a high-fundamental-repetition-rate erbium-doped all-fiber laser operating in the amplifier similariton regime. Experimental characterization shows that this laser, which is mode-locked by nonlinear polarization evolution, emits 76-fs pulses with an energy of 1.17 nJ at a repetition rate of 100 MHz. Numerical simulations support the interpretation of self-similar evolution of the pulse in the gain fiber. More specifically we introduce the concept of vector similariton in fiber lasers. The coupled x- and y- polarization components of such a pulse have a pulse profile with a linear chirp and their combined power profile evolves self-similarly when the nonlinear asymptotic regime is reached in the gain fiber.

All-fiber amplifier similariton laser based on a fiber Bragg grating filter.

This article presents, for the first time to our knowledge, an all-fiber amplifier similariton laser based on a fiber Bragg grating filter. The laser emits 2.9 nJ pulses at a wavelength of 1554 nm with a repetition rate of 31 MHz. The dechirped pulses have a duration of 89 fs. The characteristic features of the pulse profile and spectrum along with the dynamics of the laser are highlighted in representative simulations. These simulations also address the effect of the filter shape and detuning with respect to the gain spectral peak.

Automated mode locking in nonlinear polarization rotation fiber lasers by detection of a discontinuous jump in the polarization state.

A strategy to align a mode-locked fiber laser with nonlinear polarization rotation is presented. This strategy is based on measurements of the output polarization state. It is shown that, as the angle of a motorized polarization controller inside the cavity is swept, the laser eventually reaches a mode-locked regime and the values of the Stokes parameters undergo an abrupt change. The sensing of this sudden variation is thus used to detect the mode-locking condition and a feedback mechanism drives the alignment of the polarization controller to force mode locking.

Newborn pig trachea cell line cultured in air-liquid interface conditions allows a partial in vitro representation of the porcine upper airway tissue.

BACKGROUND: The domestic pig is an excellent animal model to study human microbial diseases due to its similarity to humans in terms of anatomy, physiology, and genetics. We assessed the suitability of an in vitro air-liquid interface (ALI) culture system for newborn pig trachea (NPTr) cells as a practical tool for analyzing the immune response of respiratory epithelial cells to aggressors. This cell line offers a wide microbial susceptibility spectrum to both viruses and bacteria. The purpose of our study was to evaluate and characterize diverse aspects of cell differentiation using different culture media. After the NPTr cells reached confluence, the apical medium was removed and the cells were fed by medium from the basal side. RESULTS: We assessed the cellular layer's capacity to polarize and differentiate in ALI conditions. Using immunofluorescence and electronic microscopy we evaluated the presence of goblet and ciliated cells, the epithelial junction organization, and the transepithelial electrical resistance. We found that the cellular layer develops a variable density of mucus producing cells and acquires a transepithelial resistance. We also identified increased development of cellular junctions over the culture period. Finally, we observed variable expression of transcripts associated to proteins such as keratin 8, mucins (MUC1, MUC2, and MUC4), occludin, and villin 1. CONCLUSIONS: The culture of NPTr cells in ALI conditions allows a partial in vitro representation of porcine upper airway tissue that could be used to investigate some aspects of host/respiratory pathogen interactions.

Innate immune response to a H3N2 subtype swine influenza virus in newborn porcine trachea cells, alveolar macrophages, and precision-cut lung slices.

Viral respiratory diseases remain of major importance in swine breeding units. Swine influenza virus (SIV) is one of the main known contributors to infectious respiratory diseases. The innate immune response to swine influenza viruses has been assessed in many previous studies. However most of these studies were carried out in a single-cell population or directly in the live animal, in all its complexity. In the current study we report the use of a trachea epithelial cell line (newborn pig trachea cells - NPTr) in comparison with alveolar macrophages and lung slices for the characterization of innate immune response to an infection by a European SIV of the H3N2 subtype. The expression pattern of transcripts involved in the recognition of the virus, interferon type I and III responses, and the host-response regulation were assessed by quantitative PCR in response to infection. Some significant differences were observed between the three systems, notably in the expression of type III interferon mRNA. Then, results show a clear induction of JAK/STAT and MAPK signaling pathways in infected NPTr cells. Conversely, PI3K/Akt signaling pathways was not activated. The inhibition of the JAK/STAT pathway clearly reduced interferon type I and III responses and the induction of SOCS1 at the transcript level in infected NPTr cells. Similarly, the inhibition of MAPK pathway reduced viral replication and interferon response. All together, these results contribute to an increased understanding of the innate immune response to H3N2 SIV and may help identify strategies to effectively control SIV infection.